U.S. patent application number 17/296726 was filed with the patent office on 2022-02-03 for device for distributing a flow.
The applicant listed for this patent is Cytiva Sweden AB. Invention is credited to Kerstin Erickson, Tim Francois, Klaus Gebauer, Andreas Lundin, Bjorn Olovsson.
Application Number | 20220033750 17/296726 |
Document ID | / |
Family ID | 65147321 |
Filed Date | 2022-02-03 |
United States Patent
Application |
20220033750 |
Kind Code |
A1 |
Lundin; Andreas ; et
al. |
February 3, 2022 |
Device for Distributing a Flow
Abstract
A flow distribution device for bioprocess systems, comprising: a
flow distribution manifold (12; 112) comprising: at least four
fluid connection conduits (14), wherein each fluid connection
conduit (14) comprises a first end (18) for fluid connection and an
opposite second end (20), and wherein at least three of the fluid
connection conduits comprise a membrane (19a) and a valve seat
(19b), which membrane (19a) can be put in at least two different
positions in relation to the valve seat (19b) for allowing or
preventing fluid flow between the first end (18) and the second end
(20) of the fluid connection conduit (14); and a central common
compartment (30) to which the second ends (20) of each of the fluid
connection conduits (14) are connected, whereby the first ends (18)
of each of the fluid connection conduits (14) can be in fluid
communication with the central common compartment (30) and wherein
the fluid connection conduits (14) are entering the central common
compartment (30) from at least three different directions; wherein
said flow distribution device (10) further comprises at least three
membrane actuation members (41) which are provided in connection
with one membrane (19a) of the flow distribution manifold (12; 112)
each, wherein each of said membrane actuation members (41) is
configured for actuating the membrane (19a) to be in at least two
different positions in relation to the valve seat (19b), wherein a
first position of the membrane (19a) allows flow between the first
end (18) and the second end (20) of the fluid connection conduit
(14) and a second position of the membrane (19a) prevents flow
between the first end (18) and the second end (20) of the fluid
connection conduit (14).
Inventors: |
Lundin; Andreas; (Uppsala,
SE) ; Olovsson; Bjorn; (Uppsala, SE) ;
Gebauer; Klaus; (Uppsala, SE) ; Francois; Tim;
(Uppsala, SE) ; Erickson; Kerstin; (Uppsala,
SE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Cytiva Sweden AB |
Uppsala |
|
SE |
|
|
Family ID: |
65147321 |
Appl. No.: |
17/296726 |
Filed: |
December 10, 2019 |
PCT Filed: |
December 10, 2019 |
PCT NO: |
PCT/EP2019/084322 |
371 Date: |
May 25, 2021 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
F16K 11/022 20130101;
G01N 2030/205 20130101; C12M 23/28 20130101; B01D 15/08 20130101;
F16K 11/22 20130101; C12M 41/40 20130101; C12M 23/40 20130101; F16K
27/0236 20130101; F16K 7/126 20130101; C12M 23/26 20130101; F16K
31/1266 20130101 |
International
Class: |
C12M 1/00 20060101
C12M001/00; C12M 1/34 20060101 C12M001/34 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 19, 2018 |
GB |
1820691.2 |
Claims
1. A flow distribution device for bioprocess systems, comprising: a
flow distribution manifold comprising: at least four fluid
connection conduits, wherein each fluid connection conduit
comprises a first end for fluid connection and an opposite second
end, and wherein at least three of the fluid connection conduits
comprise a membrane and a valve seat which membrane can be put in
at least two different positions in relation to the valve seat for
allowing or preventing fluid flow between the first end and the
second end of the fluid connection conduit; and a central common
compartment to which the second ends of each of the fluid
connection conduits are connected, whereby the first ends of each
of the fluid connection conduits can be in fluid communication with
the central common compartment and wherein the fluid connection
conduits are entering the central common compartment from at least
three different directions; wherein said flow distribution device
further comprises at least three membrane actuation members which
are provided in connection with one membrane of the flow
distribution manifold each, wherein each of said membrane actuation
members is configured for actuating the membrane to be in at least
two different positions in relation to the valve seat, wherein a
first position of the membrane allows flow between the first end
and the second end of the fluid connection conduit and a second
position of the membrane prevents flow between the first end and
the second end of the fluid connection conduit.
2. The flow distribution device according to claim 1, wherein at
least five or at least six fluid connection conduits are provided
in the flow distribution manifold.
3. The flow distribution device according to claim 1, wherein the
fluid connection conduits are entering the central common
compartment from at least four or at least five different
directions.
4. The flow distribution device according to claim 1, wherein the
second ends of the fluid connection conduits are connected to the
central common compartment distributed around an enclosing wall of
the central common compartment, which enclosing wall is enclosing
an inner room of the central common compartment, wherein each of
the fluid connection conduits can be in fluid communication with
the inner room of the central common compartment and wherein the
fluid connection conduits are entering the enclosing wall of the
central common compartment from at least three or at least four or
at least five different directions.
5. The flow distribution device according to claim 1, wherein
distances between the second ends of each of the fluid connection
conduits and a central point of the central common compartment will
not differ by more than 3 or 2 or 1 times an inner diameter of the
fluid connection conduits or wherein a distance between the second
end of each of the fluid connection conduits and a central point of
the central common compartment is substantially the same for each
fluid connection conduit.
6. The flow distribution device according to claim 1, wherein the
flow distribution device comprises either the same number of
membrane actuation members as the number of fluid connection
conduits provided in the flow distribution manifold or one less,
wherein one membrane actuation member is provided in connection
with each fluid connection conduit or with each fluid connection
conduit except one, whereby the flow through either all fluid
connection conduits or all except one can be controlled by a
membrane actuation member.
7. The flow distribution device according to claim 1, wherein said
flow distribution manifold is a single-use component.
8. The flow distribution device according to claim 1, wherein said
membrane actuation members are pressure controlling members.
9. The flow distribution device according to claim 1, wherein said
membrane actuation members are configured for being controlled by a
connected control system, whereby the membrane actuation members
can be controlled to actuate the membranes such that the first end
of one of the fluid connection conduits can be fluidly connected
with the first end of another one of the fluid connection
conduits.
10. The flow distribution device according to claim 1, wherein each
membrane is a double-layered membrane.
11. A bioprocess separation system comprising a separation device
and at least one flow distribution device according to claim 1
connected to an inlet and/or an outlet of the separation
device.
12. The bioprocess separation system according to claim 11, wherein
the flow distribution device is connected to an inlet of the
separation device, wherein one fluid connection conduit of the flow
distribution device is connected to the inlet of the separation
device and at least three fluid connection conduits of the flow
distribution device are connected to different fluid sources
comprising fluids to be fed to the separation device.
13. The bioprocess separation system according to claim 11, wherein
a flow distribution device is connected to an outlet of the
separation device, wherein one fluid connection conduit of the flow
distribution device is connected to the outlet of the separation
device and at least three fluid connection conduits of the flow
distribution device are connected to different fraction collectors
collecting different fractions from the separation device.
14. The bioprocess separation system according to claim 11, wherein
the bioprocess separation system comprises a) a reusable part
comprising the membrane actuation members of the flow distribution
device and at least one pump head and b) a single-use part
comprising a single use flow path comprising the flow distribution
manifold of the flow distribution device and optionally the
separation device.
15. A flow distribution manifold, comprising: at least four fluid
connection conduits, wherein each fluid connection conduit
comprises a first end for fluid connection and an opposite second
end, and wherein at least three of the fluid connection conduits
comprise a membrane and a valve seat, which membrane can be put in
at least two different positions in relation to the valve seat for
allowing or preventing fluid flow between the first end and the
second end of the fluid connection conduit; and a central common
compartment to which the second ends of each of the fluid
connection conduits are connected, whereby the first ends of each
of the fluid connection conduits can be in fluid communication with
the central common compartments and wherein the fluid connection
conduits are entering the central common compartment from at least
three different directions, wherein said flow distribution manifold
is configured for being used in a flow distribution device
according to claim 1.
16. The flow distribution manifold according to claim 15, wherein
at least five or at least six fluid connection conduits are
provided in the flow distribution manifold.
17. The flow distribution manifold according to claim 15, wherein
the fluid connection conduits are entering the central common
compartment from at least four or at least five different
directions.
18. The flow distribution manifold according to claim 15, wherein
the second ends of the fluid connection conduits are connected to
the central common compartment distributed around an enclosing wall
of the central common compartment, which enclosing wall is
enclosing an inner room of the central common compartment, wherein
each of the fluid connection conduits can be in fluid communication
with the inner room of the central common compartment and wherein
the fluid connection conduits are entering the enclosing wall of
the central common compartment from at least three or at least four
or at least five different directions.
19. The flow distribution manifold according to claim 15, wherein
distances between the second ends of each of the fluid connection
conduits and a central point of the central common compartment will
not differ by more than 3 or 2 or 1 times an inner diameter of the
fluid connection conduits or wherein a distance between the second
end of each of the fluid connection conduits and a central point of
the central common compartments is substantially the same for each
fluid connection conduit.
20. The flow distribution manifold according to claim 15, wherein a
distance from the second end of at least one of the fluid
connection conduits to a second end of an adjacent fluid connection
conduit is smaller than the distance between central points of two
membranes provided to the same two fluid connection conduits.
21. The flow distribution manifold according to claim 15, wherein
said flow distribution manifold is a single-use component.
22. A single use flow path configured to be used in the bioprocess
separation system according to claim 11 and comprising a flow
distribution manifold configured to be used in a flow distribution
device.
23. The single use flow path according to claim 22, wherein said
single use flow path is pre-sterilized.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to a flow distribution device,
a flow distribution manifold, a bioprocess separation system and a
single use flow path for bioprocess systems.
BACKGROUND
[0002] Valve operated fluid delivery devices are for example used
in liquid handling systems applied in the bioprocess field, for
example in chromatography systems or filter systems. The valves can
e.g. be diaphragm valves or pinch valves. For example at an inlet
to a chromatography column there may be a need to connect a number
of different fluid sources, such as for example different samples,
washing fluids and elution fluid. Likewise, at an outlet of a
chromatography column there may be a need to connect to a number of
different fraction collectors. Diaphragm valves may be used in such
liquid handling systems. A schematic illustration of a liquid
handling system using diaphragm valves according to prior art is
shown in FIG. 1. Four fluid modules 300 each comprising a T-shaped
fluid conduit 302, two diaphragm valves 304 and two connectors 306
are shown connected to each other and to an external fluid conduit
308 and a pump P. With such a liquid handling system, four
different fluid sources can for example be connected to an inlet of
a chromatography system and, thanks to the provision of two
diaphragm valves for each fluid source inlet, backflow and mixing
can be avoided.
[0003] A problem with such a liquid handling system is that it is
complex and comprises many valves. It may also be difficult to
clean.
SUMMARY
[0004] An object of the present invention is to provide an improved
flow distribution device.
[0005] A further object of the invention is to provide a flow
distribution device with reduced risk for contamination and carry
over.
[0006] This is achieved by a flow distribution device, a flow
distribution manifold, a bioprocess separation system and a single
use flow path according to the independent claims.
[0007] According to one aspect of the invention a flow distribution
device for bioprocess systems is provided. Said flow distribution
device comprises: [0008] a flow distribution manifold comprising:
[0009] at least four fluid connection conduits, wherein each fluid
connection conduit comprises a first end for fluid connection and
an opposite second end, and wherein at least three of the fluid
connection conduits comprise a membrane and a valve seat, which
membrane can be put in at least two different positions in relation
to the valve seat for allowing or preventing fluid flow between the
first end and the second end of the fluid connection conduit; and
[0010] a central common compartment to which the second ends of
each of the fluid connection conduits are connected, whereby the
first ends of each of the fluid connection conduits can be in fluid
communication with the central common compartment and wherein the
fluid connection conduits are entering the central common
compartment from at least three different directions; [0011]
wherein said flow distribution device further comprises [0012] at
least three membrane actuation members which are provided in
connection with one membrane of the flow distribution manifold
each, wherein each of said membrane actuation members is configured
for actuating the membrane to be in at least two different
positions in relation to the valve seat, wherein a first position
of the membrane allows flow between the first end and the second
end of the fluid connection conduit and a second position of the
membrane prevents flow between the first end and the second end of
the fluid connection conduit.
[0013] According to another aspect of the invention a flow
distribution manifold is provided comprising: [0014] at least four
fluid connection conduits, wherein each fluid connection conduit
comprises a first end for fluid connection and an opposite second
end, and wherein at least three of the fluid connection conduits
comprise a membrane and a valve seat, which membrane can be put in
at least two different positions in relation to the valve seat for
allowing or preventing fluid flow between the first end and the
second end of the fluid connection conduit; and [0015] a central
common compartment to which the second ends of each of the fluid
connection conduits are connected, whereby the first ends of each
of the fluid connection conduits can be in fluid communication with
the central common compartment and wherein the fluid connection
conduits are entering the central common compartment from at least
three different directions, [0016] wherein said flow distribution
manifold is configured for being used in a flow distribution device
as described above.
[0017] According to another aspect of the invention a bioprocess
separation system is provided comprising a separation device and at
least one flow distribution device as described above connected to
an inlet and/or an outlet of the separation device.
[0018] According to another aspect of the invention a single-use
flow path is provided which is configured to be used in a
bioprocess separation system as described above and comprising a
flow distribution manifold as described above which is configured
to be used in a flow distribution device as described above.
[0019] Hereby a flow distribution device is provided with a reduced
number of diaphragm valves compared to prior art devices.
Furthermore, cleaning of the flow distribution device is
facilitated and the risk for contamination and carry over is hereby
decreased thanks to the design comprising a central common
compartment into which the fluid connections are entering from
different directions, i.e. there is a common compartment provided
in the middle of the device. Hereby a "distance" between different
connections can be the same.
[0020] In one embodiment of the invention at least five fluid
connection conduits are provided in the flow distribution manifold.
In another embodiment of the invention at least six fluid
connection conduits are provided in the flow distribution
manifold.
[0021] In one embodiment of the invention the fluid connection
conduits are entering the central common compartment from at least
four different directions. In another embodiment of the invention
the fluid connection conduits are entering the central common
compartment from at least five different directions.
[0022] In one embodiment of the invention the second ends of the
fluid connection conduits are connected to the central common
compartment distributed around an enclosing wall of the central
common compartment, which enclosing wall is enclosing an inner room
of the central common compartment, wherein each of the fluid
connection conduits can be in fluid communication with the inner
room of the central common compartment and wherein the fluid
connection conduits are entering the enclosing wall of the central
common compartment from at least three different directions. In
another embodiment the fluid connection conduits are entering the
enclosing wall of the central common compartment from at least four
different directions and in another embodiment the fluid connection
conduits are entering the enclosing wall of the central common
compartment from at least five different directions.
[0023] In one embodiment of the invention distances between the
second ends of each of the fluid connection conduits and a central
point of the central common compartment will not differ by more
than 3 or 2 or 1 times an inner diameter (ID) of the fluid
connection conduits. In one embodiment of the invention a distance
between the second end of each of the fluid connection conduits and
a central point of the central common compartment is substantially
the same for each fluid connection conduit.
[0024] In one embodiment of the invention the flow distribution
device comprises either the same number of membrane actuation
members as the number of fluid connection conduits provided in the
flow distribution manifold or one less, wherein one membrane
actuation member is provided in connection with each fluid
connection conduit or with each fluid connection conduit except
one, whereby the flow through either all fluid connection conduits
or all except one can be controlled by a membrane actuation
member.
[0025] In one embodiment of the invention said flow distribution
manifold is a single-use component.
[0026] In one embodiment of the invention said membrane actuation
members are pressure controlling members.
[0027] In one embodiment of the invention said membrane actuation
members are configured for being controlled by a connected control
system, whereby the membrane actuation members can be controlled to
actuate the membranes such that the first end of one of the fluid
connection conduits can be fluidly connected with the first end of
another one of the fluid connection conduits.
[0028] In one embodiment of the invention a flow distribution
device is connected to an inlet of the separation device, wherein
one fluid connection conduit of the flow distribution device is
connected to the inlet of the separation device and at least three
fluid connection conduits of the flow distribution device are
connected to different fluid sources comprising fluids to be fed to
the separation device.
[0029] In one embodiment of the invention a flow distribution
device is connected to an outlet of the separation device, wherein
one fluid connection conduit of the flow distribution device is
connected to the outlet of the separation device and at least three
fluid connection conduits of the flow distribution device are
connected to different fraction collectors collecting different
fractions from the separation device.
[0030] In one embodiment of the invention the bioprocess separation
system comprises a reusable part comprising the membrane actuation
members of the flow distribution device and at least one pump head
and a single-use part comprising a single use flow path comprising
the flow distribution manifold of the flow distribution device and
optionally the separation device.
[0031] In one embodiment of the invention said single use flow path
is pre-sterilized.
BRIEF DESCRIPTION OF DRAWINGS
[0032] FIG. 1 shows schematically a device for delivery of fluid
according to prior art.
[0033] FIG. 2a is an exploded perspective view of a flow
distribution device comprising a flow distribution manifold
according to one embodiment of the invention.
[0034] FIG. 2b is a cross section side view of the flow
distribution manifold as shown in FIG. 2a as mounted.
[0035] FIG. 2c is a top view of the flow distribution manifold as
shown in FIGS. 2a and 2b without a cover and without membranes.
[0036] FIG. 2d is a perspective view of the flow distribution
manifold as shown in FIGS. 2a-2c as mounted.
[0037] FIG. 3a is an exploded perspective view of a flow
distribution device comprising a flow distribution manifold
according to another embodiment of the invention.
[0038] FIG. 3b is a cross section along the dotted lines in FIG. 3c
of the flow distribution manifold as shown in FIG. 3a as
mounted.
[0039] FIG. 3c is a top view of the flow distribution manifold as
shown in FIGS. 3a and 3b without a cover and without membranes.
[0040] FIG. 3d is a perspective view of the flow distribution
manifold as shown in FIGS. 3a-3c as mounted.
[0041] FIG. 4 shows schematically a bioprocess separation system in
which a flow distribution device according to the invention can be
used.
[0042] FIG. 5 shows a double-layer membrane according to an
embodiment of the invention.
DETAILED DESCRIPTION OF EMBODIMENTS
[0043] FIGS. 2a-2d show views of a fluid distribution device 10 and
a fluid distribution manifold 12 according to one embodiment of the
invention. FIGS. 3a-3d show different views of a fluid distribution
device 110 and a fluid distribution manifold 112 according to
another embodiment of the invention. FIGS. 2a and 3a show exploded
perspective views of the fluid distribution device 10; 110, FIGS.
2b and 3b are cross section side views of the fluid distribution
manifolds 12; 112 along the dotted lines of FIGS. 2c and 3c
respectively. FIGS. 2c and 3c are top views of the fluid
distribution manifolds 12; 112 without membranes provided and FIGS.
2d and 3d are perspective view of the fluid distribution manifolds
12; 112 as mounted. The two different embodiments will be described
together below and the same reference numbers will be used for
corresponding parts in the two different embodiments.
[0044] The fluid distribution device 10; 110 comprises one part
which can be a single-use part. This is called a fluid distribution
manifold 12; 112 and comprises at least four fluid connection
conduits 14. In another embodiment the fluid distribution manifold
comprises at least five or at least six fluid connection conduits
14. Each fluid connection conduit 14 comprises a first end 18 for
fluid connection and an opposite second end 20. In the embodiment
as shown in FIGS. 2a-2d eight fluid connection conduits 14 are
shown and in the embodiment as shown in FIGS. 3a-3d nine fluid
connection conduits 14 are shown, however the number of fluid
connection conduits can of course be different. In FIG. 2b two of
the eight fluid connection conduits 14 of this embodiment are shown
in cross section. The first ends 18 and the second ends 20 of these
two fluid connection conduits 14 can also be seen in FIG. 2b. In
FIG. 3a, nine fluid connection conduits 14 can be seen. In FIGS. 2d
and 3d, all the first ends 18 of the fluid connection conduits 14
can be seen. In one embodiment of the invention at least all fluid
connection conduits 14 except one comprise a membrane 19a and a
valve seat 19b, which membrane 19a can be put in at least two
different positions in relation to the valve seat 19b for allowing
or preventing fluid flow between the first end 18 and the second
end 20 of this fluid connection conduit 14. In alternative
language, membrane 19a is movable between an open position (at a
distance from valve seat 19b) and a closed position (in sealing
abutment with valve seat 19b). In the open position, fluid flow
between first end 18 and second end 20 is allowed and in the closed
position it is prevented. Of course also all fluid connection
conduits 14 can comprise a membrane 19a and a valve seat 19b or
optionally also all fluid conduits except two comprise a membrane
19a and a valve seat 19b. It can also be expressed, as in the
claims, that at least three of the fluid connection conduits 14
when there are at least four fluid connection conduits 14 comprise
a membrane 19a and a valve seat 19b. Actuation of the membranes 19a
into the at least two different positions is provided from membrane
actuation members 41 provided in the fluid distribution device 10;
110 as will be further described below.
[0045] In certain embodiments, the membranes 19a, such as each
membrane 19a, may comprise double-layered membranes. As shown in
FIG. 5, a membrane 19a can then comprise the two membrane
components 19a' and 19a''. This mitigates the risk for
inappropriate fluid flows in case one membrane component ruptures.
Further, the components 19a' and 19a'' may be spaced apart by a
pattern of spacer elements 200, which can e.g. be studs, pillars,
ribs etc. In the space 201 between the components a fluid sensor
202 (e.g. a conductivity sensor, pressure sensor etc.) can then be
inserted to detect the presence of fluid due to the rupture of one
of the components 19a' and 19a''.
[0046] According to the invention the fluid distribution manifold
12; 112 further comprises a central common compartment 30 to which
the second ends 20 of each of the fluid connection conduits 14 are
connected, whereby the first ends 18 of each of the fluid
connection conduits 14 can be in fluid communication with the
central common compartment 30, i.e. when the corresponding
membranes 19a are in the first (open) position. Furthermore,
according to the invention the fluid connection conduits 14 are
entering the central common compartment 30 from at least three
different directions. In another embodiment of the invention the
fluid connection conduits 14 are entering the central common
compartment 30 from at least four or at least five different
directions. In the embodiments shown in FIGS. 2a-2d and in FIGS.
3a-3d all the fluid connection conduits 14 are entering the central
common compartment 30 from different directions and the fluid
distribution manifold 12 has a star-like configuration with the
fluid connection conduits 14 pointing away from the central common
compartment 30 in different directions. In the embodiments shown in
FIGS. 2 and 3 the fluid connection conduits 14 are all provided in
one and the same plane when entering into the central common
compartment 30 but they could as well be provided in different
planes, i.e. the second ends 20 of the fluid connection conduits 14
can be connected to the central common compartment 30 distributed
around an enclosing wall 33 of the central common compartment 30,
which enclosing wall 33 is enclosing an inner room 35 of the
central common compartment 30, wherein each of the fluid connection
conduits 14 can be in fluid communication with the inner room 35 of
the central common compartment 30, when the corresponding membranes
19a are in the first (open) position), and wherein the fluid
connection conduits 14 are entering the enclosing wall 33 of the
central common compartment 30 from at least two or three or four
different directions. In the embodiments of the invention shown in
FIGS. 2 and 3 the fluid connection conduits 14 are entering the
enclosing wall 33 of the central common compartment 30 from eight
and nine different directions respectively. As discussed above,
fluid connection conduits could as well be provided entering the
central common compartment 30 from all directions, i.e. for example
entering the central common compartment in a direction being
substantially perpendicular in relation to the fluid connection
conduits as shown in FIGS. 2 and 3. The central common compartment
30 can have a form of a sphere or a spheroid which is the case in
the embodiment as shown in FIGS. 2a-2d or be annular as is the case
in the embodiment shown in FIGS. 3a-3d.
[0047] The flow distribution device 10; 110 further comprises at
least three membrane actuation members 41 which are provided in
connection with one membrane 19a of the flow distribution manifold
12; 112 each. In the embodiment of the invention as shown in FIGS.
2a-2d one membrane actuation member 41 is provided for each fluid
connection conduit 14, i.e. eight membrane actuation members 41 are
provided in the flow distribution device 12. In the embodiment of
the invention as shown in FIGS. 3a-3d all fluid connection conduits
14 except one are provided with a membrane actuation member 41.
[0048] Each of said membrane actuation members 41 is configured for
actuating the membrane 19a to be in at least two different
positions in relation to the valve seat 19b, wherein a first
position of the membrane 19a allows flow between the first end 18
and the second end 20 of the fluid connection conduit 14 and a
second position of the membrane 19a prevents flow between the first
end 18 and the second end 20 of the fluid connection conduit
14.
[0049] The membrane actuation members 41 can be for example
pressure controlling members such as tubes through which
pressurized air or suction can be provided. Hereby the membranes
can be controlled into the at least two different positions by
controlling pressure in the membrane actuation members 41. Another
alternative of membrane actuation members 41 can be some kind of
rods in mechanical connection with the membranes whereby a
displacement of the rod can be transferred to displacement of the
membranes.
[0050] The membrane actuation members 41 can be configured for
being controlled by a connected control system, whereby the
positions of the membranes 19a in the fluid distribution manifold
12; 112 can be controlled form the control system such that the
first end 18 of one of the fluid connection conduits 14 can be
fluidly connected with the first end 18 of another one of the fluid
connection conduits 14. In one embodiment of the invention the
first end 18 of any one of the different fluid connection conduits
14 can be connected with the first end 18 of any one of the other
fluid connection conduits 14.
[0051] The membranes 19a and valve seats 19b are suitably provided
at a position of the fluid connection conduits 14 close to the
second ends 20 of the fluid connection conduits 14. The distance d1
between the valve seat 19b and the second end 20 of the fluid
connection conduit 14 can for example be less than four or less
than three or less than two fluid connection tube 14 inner
diameters ID.
[0052] In some embodiments of the invention the distances between
the second ends 20 of each of the fluid connection conduits 14 and
a central point 37 of the central common compartment 30 will not
differ by more than 3 or 2 or 1 times an inner diameter, ID, of the
fluid connection conduits 14. In the embodiments as shown in FIGS.
2a-2d and in FIGS. 3a-3d the central common compartment 30 is
symmetrical and the fluid connection conduits 14 are positioned
symmetrical around the central common compartment 30 at
substantially the same distance from a central point 37 of the
central common compartment 30, i.e. a distance between the second
end 20 of each of the fluid connection conduits 14 and a central
point 37 of the central common compartment 20 is substantially the
same for each fluid connection conduit 14.
[0053] A difference from prior art flow delivery manifolds is that
in prior art the fluid connections were provided in parallel while
in this new invention at least some of the fluid connection
conduits are provided in different directions, i.e. at least some
of the fluid connection conduits 14 are spread out from the central
common compartment 30. Hereby a distance from a center of the
second end 20 of at least one of the fluid connection conduits 14
to a center of the second end 20 of an adjacent fluid connection
conduit 14 is smaller than the distance between central points of
two membranes 19a provided to the same two fluid connection
conduits 14.
[0054] The flow distribution manifold 12; 112 can be a single-use
component. It can be molded from a suitable material, such as for
example a polymer, and it can be provided with aseptic connectors
for aseptic connection in a system. The flow distribution manifold
12; 112 can be pre-sterilized for example by gamma radiation or
other sterilization methods, optionally together with other parts
of a single-use flow path to be used for example in a bioprocess
separation system, such as a chromatography system or a filter
system as will be further described below.
[0055] Another part of the flow distribution device 10; 110 can be
a reusable part and this part comprises the membrane actuation
members 41.
[0056] The flow distribution manifold 12; 112 can comprise three
parts as disclosed in the exploded views is FIGS. 2a and 3a. A
first part 20a comprises the fluid connection conduits 14, the
valve seats 19b and the common compartment 30. In both the
embodiment shown in FIGS. 2a-2d and the embodiment shown in FIGS.
3a-3d one of the fluid connection conduits 14 has its first end 18
entering towards a side edge 22a of the first part 20a and all the
other fluid connection conduits 14 have their first ends 18
entering towards a bottom side 22b of the first part 20a, see FIGS.
2d and 3d. This may be suitable when connecting the fluid
distribution device 10; 110 in a system, for example to an inlet or
an outlet of a bioprocess separation system as will be further
described in relation to FIG. 4 below. A second part 20b of the
flow distribution manifold 12; 112 comprises the membranes 19a and
a third part 20c of the flow distribution manifold 12; 112
comprises connections 24 for allowing connection to membrane
actuation members 41 and mating them to one membrane 19a each.
[0057] The present invention also relates to a bioprocess
separation system 71 as schematically shown in FIG. 4, such as a
chromatography system or a filter system, which comprises one or
more fluid distribution devices 10; 110 as described above. One
fluid distribution device 10; 110 can be connected to an inlet 75
of a separation device 73 provided in the bioprocess separation
system 71 and/or one fluid distribution device 10; 110 can be
connected to an outlet 77 of the separation device 73. The
separation device 73 can for example be a chromatography column or
a filter. At least one pump 79 is also provided in the bioprocess
separation system 71. Other components such as valves and sensors
are normally also provided in the bioprocess separation system 71
but will not be described in further detail here. A single-use flow
path 81 comprising flow paths, the flow distribution manifold 12;
112 according to the invention and optionally also the separation
device 73 is also part of the present invention, i.e. the flow
distribution manifold 12; 112 can be connected to other flow paths
of a bioprocess separation system and be pre-sterilized for easy
connection and exchange in a bioprocess separation system 71.
Reusable parts of the bioprocess separation system 71 are for
example pump heads 79 and the membrane actuation members 41 of the
flow distribution device 10; 110.
[0058] The central common compartment 30 of the fluid distribution
manifold 12; 112 according to the invention can optionally be
provided with a sensor, for example an air sensor, pressure sensor
or a conductivity sensor.
[0059] The fluid distribution device 10; 110 according to the
invention is compact and flexible. It can be positioned remote from
a system where it is used because of the valve control provided by
pressurized air.
[0060] As discussed above the flow distribution manifold is
suitable for single-use applications. The flow distribution
manifold, and optionally a single use flow path to which it can be
connected, can be pre-sterilized by for example gamma radiation and
can be provided with aseptic connectors for aseptic connection in a
system.
[0061] The single-use technology (SUT) is important in the
bioprocess industry in order to reduce production cost, increase
production throughput and quality and to increase safety. With
single-use processing technology and equipment, wetted parts that
are in contact with the process fluid and drug product during
processing, such as for example fluid storage vessels, tubing,
separation equipment etc., are provided as clean and ready to use
consumables which are to be installed and used for a specific
process, product or over a limited time only and to be disposed
thereafter.
[0062] SUT consumables are typically produced, configured and
packaged in clean room environments to avoid contamination with
microorganisms, particulates etc. SUT wetted parts can further be
provided clean and pre-sterilized, thus allowing for aseptic and/or
sterile processing, hereby reducing above mentioned risks relevant
for product, operator or patient safety. Typically, SUT wetted
parts are subjected to a sterilizing gamma irradiation treatment
prior to use in the biomanufacturing process, and when doing so
they are deployed as `pre-sterilized` at the point of use. This may
involve providing the consumable with a formal and validated
sterile claim after the sterilizing treatment, however, it may
alternatively involve providing a consumable that has undergone a
sterilizing treatment but is provided without a formal sterile
claim. With controlled and rigorous manufacturing conditions, SUT
consumables may also be deployed non-sterile and/or with treatments
that controls the state and condition of the consumable. Hereby,
contamination levels by microorganisms, generally called
`bioburden`, or levels of contamination or presence of
contaminating substances or particles may be controlled and
maintained within pre-defined levels.
[0063] The advantage of using single-use technology (SUT) fluid
handling equipment is primarily that cross-contamination in between
production batches and campaigns is eliminated when the SUT
equipment is used for a single drug product only. The SUT equipment
is disposed of after use, which can be after a single run, batch or
campaign comprising multiple runs and batches. When providing SUT
equipment pre-sterilized or by other means bioburden controlled,
initial cleaning and sanitization (for example by contacting the
flow path with sodium hydroxide solutions) or sterilization can be
avoided. This enables a LEAN manufacturing approach, because time
consuming, costly and non-value adding steps can be omitted. When
using the SUT for a single run or batch only, even cleaning
post-use may be omitted. The elimination of cleaning procedures and
required cleaning fluids further reduces clean water requirements
to prepare cleaning solutions in the first place, fluid handling
and waste treatment, which translates to reduced facility size and
complexity.
[0064] Single-use equipment may be provided with fluid connectors
that enable closed processing and thereby protect the process fluid
line and/or the operator and environment from contamination or
exposure to hazardous substances. Alternatively, fluid connectors
may be providing aseptic connectivity features, hereby providing
strict and complete closure of the fluid lines. When using aseptic
connectors or disconnectors, sterility of a fluid line, two
connected lines or components, or two disconnected lines or
components can be maintained, provided that the fluid lines or
components involved in the operation have been provided sterile.
With these features, SUT equipment allows not only for more
efficient processing, it may also allow for reducing requirements
on classification and containment of facilities, thereby reducing
cost and risk for contamination or infection of the process fluid
and drug product, and/or contamination and infection of the process
environment, facility or the operator.
[0065] SUT systems provide higher flexibility in (re-)configuring a
manufacturing facility and adapting it to different processes and
products by design, i.e. through the reduced need for fixed
installations compared to traditional processing systems and
installations, which for example required auxiliary systems for CIP
(Cleaning in Place) and SIP (Sterilization in place). Nowadays, SUT
equipment and SUT processing regimes are therefore available or are
being made available for the majority of all types of equipment
and/or unit operations, among them bioreactors for cell culture or
fermentation, buffer bags for liquid storage, tubing and pumps for
liquid transfer and filling operations, filters, chromatography
columns and related systems for separations.
[0066] With these features, SUT equipment does provide improved
efficiency, safety and convenience compared to traditional
installations and systems. Traditional installations and systems
for processing are typically made from stainless steel and/or
plastic and are not produced under controlled (or clean room)
conditions reducing bioburden. Traditional systems are typically
cleaned in place (CIP), sometimes also sterilized in place (SIP),
which not only requires auxiliary installations, equipment and
fluids, but involves also substantial time for validation,
execution, and quality control of CIP and SIP procedures. The size,
cost and complexity of facilities relying on traditional equipment
and installations is significantly larger compared to production
facilities deploying SUT. SUT facilities and processes can be
planned, built and started up in significantly shorter time
compared to traditional manufacturing technology, and SUT reduces
capital investments and financial risk associated with a typically
highly dynamic portfolio of drug products as well as risk and
uncertainty related to the testing and approval of drug candidates
and their product demand.
* * * * *